Genetics of cardiovascular disease

Question 1

What are the main genetic causes of congenital heart disease (CHD)?

Answer 1

🔹 Single-gene disorders (e.g., Marfan’s syndrome, Noonan syndrome)
🔹 Chromosomal abnormalities (e.g., Trisomy 21, Turner syndrome)
🔹 Microdeletion syndromes (e.g., 22q11.2 deletion in DiGeorge syndrome)

Question 2

What is the genetic basis of Marfan’s Syndrome?

Answer 2

🔹 Autosomal dominant inheritance
🔹 Mutation in FBN1 gene (fibrillin-1)
🔹 Affects connective tissue → Aortic aneurysm & mitral valve prolapse

Question 3

What is the genetic basis of Dilated Cardiomyopathy (DCM)?

Answer 3

🔹 Often autosomal dominant
🔹 Mutations in TTN (Titin), LMNA, MYH7 genes
🔹 Leads to ventricular dilation & systolic dysfunction

Question 4

What is the genetic basis of Long QT Syndrome (LQTS)?

Answer 4

🔹 Caused by mutations in ion channel genes (e.g., KCNQ1, KCNH2, SCN5A)
🔹 Prolonged QT interval → Risk of Torsades de Pointes & sudden death
🔹 Can be autosomal dominant or recessive

Question 5

What is the genetic basis of Familial Hypercholesterolemia (FH)?

Answer 5

🔹 Autosomal dominant inheritance
🔹 Mutations in LDLR, APOB, PCSK9 genes
🔹 Leads to high LDL cholesterol → Atherosclerosis & early heart disease

Question 6

What are common chromosomal disorders linked to CHD?

Answer 6

✅ Trisomy 21 (Down Syndrome) – AV septal defects
✅ Trisomy 18 (Edwards Syndrome) – VSD, PDA
✅ Trisomy 13 (Patau Syndrome) – VSD, ASD
✅ Turner Syndrome (45,X) – Bicuspid aortic valve, Coarctation of the aorta

Question 7

What is 22q11.2 Deletion Syndrome (DiGeorge Syndrome) & its cardiac manifestations?

Answer 7

🔹 Microdeletion syndrome affecting the TBX1 gene
🔹 Causes conotruncal heart defects (e.g., Tetralogy of Fallot, Interrupted Aortic Arch)
🔹 Other features: Cleft palate, hypocalcemia, immunodeficiency

Question 8

Why is a genetic diagnosis important in congenital heart disease?

Answer 8

🔹 Helps predict disease progression & prognosis
🔹 Aids in treatment decisions (e.g., beta-blockers in LQTS)
🔹 Enables family screening & genetic counseling

Question 9

How do you manage a family with a genetic diagnosis of CHD?

Answer 9

1️⃣ Genetic counseling (explain inheritance & recurrence risk)
2️⃣ Family screening (ECG, echocardiogram, genetic testing)
3️⃣ Prenatal diagnosis (e.g., fetal echocardiography)
4️⃣ Lifestyle advice & medical follow-up

Question 10

Mnemonic for Genetic Heart Diseases: “MAD LQF”

Answer 10

✅ Marfan’s Syndrome – FBN1 mutation
✅ Autosomal dominant Dilated Cardiomyopathy – TTN, LMNA mutations
✅ DiGeorge Syndrome – 22q11.2 deletion
✅ Long QT Syndrome – KCNQ1, KCNH2 mutations
✅ QT prolongation – Risk of sudden death
✅ Familial Hypercholesterolemia – LDLR, APOB, PCSK9 mutations